Context: Somatic or germline mutations in up to 15 disease-causative genes are detectable in up to 50% of patients with pheochromocytoma (PCC) and paraganglioma (PGL). Very recently, somatic H-RAS mutations were identified byexomesequencing in approximately7%in sporadic PCCs and PGLs, in association with male sex and benign behavior. Objective: To explore the prevalence of RAS mutations in a cohort of 271 PCC and PGL from a European registry and to compare the genotype with clinical and pathological characteristics of potential clinical interest. Setting and Design: Genetic screening for hotspot mutations in H-, N-, and K-RAS genes was performed by means of Sanger sequencing or pyrosequencing methods on tumor DNA in a series of patients with (n 107) or without (n 164) germline or somatic PCC/PGL-related gene mutations. Results: Overall, H-RAS mutations were detected in 5.2% of cases (14/271), which were confined to sporadic PCCs resulting in a prevalence of 10% (14/140) in this cohort. In contrast, no mutations were found in PCC with PCC/PGL-related gene mutations (0/76) or in PGL (0/55) harboring or not mutations in PCC/PGL susceptibility genes. In this large series, H-RAS mutations in PCCs lacked any significant correlation with pathological or basic clinical endpoints. Conclusions: Somatic H-RAS mutations are restricted to a relevant proportion of sporadic PCC. These findings provide the basis to study potential H-RAS-dependent correlations with long-term outcome data.

H-RAS mutations are restricted to sporadic pheochromocytomas lacking specific clinical or pathological features data from a multi-institutional series

RAPA, IDA;PAPOTTI, Mauro Giulio;VATRANO, SIMONA;VOLANTE, Marco
2014-01-01

Abstract

Context: Somatic or germline mutations in up to 15 disease-causative genes are detectable in up to 50% of patients with pheochromocytoma (PCC) and paraganglioma (PGL). Very recently, somatic H-RAS mutations were identified byexomesequencing in approximately7%in sporadic PCCs and PGLs, in association with male sex and benign behavior. Objective: To explore the prevalence of RAS mutations in a cohort of 271 PCC and PGL from a European registry and to compare the genotype with clinical and pathological characteristics of potential clinical interest. Setting and Design: Genetic screening for hotspot mutations in H-, N-, and K-RAS genes was performed by means of Sanger sequencing or pyrosequencing methods on tumor DNA in a series of patients with (n 107) or without (n 164) germline or somatic PCC/PGL-related gene mutations. Results: Overall, H-RAS mutations were detected in 5.2% of cases (14/271), which were confined to sporadic PCCs resulting in a prevalence of 10% (14/140) in this cohort. In contrast, no mutations were found in PCC with PCC/PGL-related gene mutations (0/76) or in PGL (0/55) harboring or not mutations in PCC/PGL susceptibility genes. In this large series, H-RAS mutations in PCCs lacked any significant correlation with pathological or basic clinical endpoints. Conclusions: Somatic H-RAS mutations are restricted to a relevant proportion of sporadic PCC. These findings provide the basis to study potential H-RAS-dependent correlations with long-term outcome data.
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Oudijk L; de Krijger RR; Rapa I; Beuschlein F; de Cubas AA; Dei Tos AP; Dinjens WN; Korpershoek E; Mancikova V; Mannelli M; Papotti M; Vatrano S; Robledo M; Volante M.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/153340
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